title: Monocyte-macrophage polarization balance in pre-diabetic individuals.
abstract: Pre-diabetes is characterized by increased cardiovascular risk and chronic inflammation. The activation of monocyte-macrophages plays major roles in vascular biology. Herein, we aimed to analyze monocyte-macrophage polarization status in subjects with IFG and/or IGT compared with normal glucose tolerant (NGT) individuals. We enrolled 87 middle-aged individuals with low prevalence of cardiovascular disease. Based on OGTT, they were divided into 49 NGT and 38 pre-diabetic (IFG and/or IGT). Using flow cytometry analysis of peripheral blood cells, we quantified traditional monocyte subsets based on CD14 and CD16 expression as well as novel monocyte-macrophage pro-inflammatory CD68(+)CCR2(+) M1 and anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 phenotypes. The M1/M2 ratio was taken to represent the polarization balance. There were no differences in traditional classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and nonclassical (CD14(+)CD16(+)) monocytes between groups. Rather, compared to NGT, pre-diabetic subjects showed a significant increase in pro-inflammatory M1 cells and percent expression of the oxLDL scavenger receptor CD68, without changes in anti-inflammatory M2 cells. M1 levels and CD68 expression were directly correlated with HbA1c. We show for the first time that otherwise healthy pre-diabetic subjects have excess M1 inflammatory cells in peripheral blood, which may contribute to cardiovascular risk.
authors.affiliation: Department of Medicine, Policlinico Universitario, Via Giustiniani, 2, 35100, Padua, Italy, gianpaolofadini@hotmail.com.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Fadini
authors.forename: Roberta
authors.initials: R
authors.lastname: Cappellari
authors.forename: Marta
authors.initials: M
authors.lastname: Mazzucato
authors.forename: Carlo
authors.initials: C
authors.lastname: Agostini
authors.forename: Saula
authors.initials: S
authors.lastname: Vigili de Kreutzenberg
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
mesh_terms: D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D001772:Blood Cell Count; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011236:Prediabetic State / Q000097:blood / Q000276:immunology*; D017452:Receptors, IgG / Q000097:blood; D012307:Risk Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; C067980:CD68 antigen, human; D000097382:CD68 Molecule